Heterogeneity of a Campylobacter jejuni Protein That Is Secreted through the Flagellar Filament

Abstract

Cj0859c, or FspA, is a small, acidic protein ofCampylobacter jejunithat is expressed by a σ28promoter. Analysis of thefspAgene in 41 isolates ofC. jejunirevealed two overall variants of the predicted protein, FspA1 and FspA2. Secretion of FspA occurs in broth-grown bacteria and requires a minimum flagellar structure. The addition of recombinant FspA2, but not FspA1, to INT407 cells in vitro resulted in a rapid induction of apoptosis. These data define a novelC. jejunivirulence factor, and the observed heterogeneity amongfspAalleles suggests alternate virulence potential among different strains.

Disruption of colonic barrier function and induction of mediator release by strains of Campylobacter jejuni that invade epithelial cells

“…This has allowed a number of virulence factors to be identified, including a number of flagellar proteins, which not only enable chemotaxis towards mucus and amino acids and epithelial cell invasion [5][6][7] , but also facilitate secretion of non-flagellar virulence proteins [6] , O-linked glycosylation, which is required for optimal flagella function [7] , proteins secreted via flagella that result in epithelial cell invasion and apoptosis [8][9][10] , a cytolethal distending toxin (CLDT) [11] with DNAse activity [12] , associated with apoptosis [13] and secretion of interleukin (IL)-8 and other chemokines [14,15] and a lipo-oligosaccharide that resembles human neuronal gangliosides, which may pre-dispose to autoimmune phenomena such as Guillain-Barre syndrome [16] . Clinical isolates vary in the extent to which they express these virulence factors.…”

Change Is Good: Variations in Common Biological Mechanisms in the Epsilonproteobacterial GeneraCampylobacterandHelicobacter

“…FspA1 and FspA2 are both secreted in a flagellum-dependent manner but are not required for invasion. Instead, FspA2 is able to induce apoptosis in INT407 cells (489). Another 28 -dependent gene involved in invasion of intestinal cells is cj0977 (217).…”

“…Even though 28 is involved mainly in expression of flagellar genes in many bacteria, C. jejuni uses 28 for expression of some genes not involved in motility (80,217,489). Instead, some of these 28 -dependent genes have been implicated in invasion or toxicity of intestinal epithelial cells (217,489).…”

“…Instead, some of these 28 -dependent genes have been implicated in invasion or toxicity of intestinal epithelial cells (217,489). One of these genes, fspA, appears as two alleles (fspA1 and fspA2) in C. jejuni strains (489).…”

“…Also potentially included as class 2 genes are fliA and flgM, which encode 28 and its anti-factor, since some evidence exists that expression of these genes is partially 54 dependent (80,650). Class 3 genes include those dependent on 28 for expression, which include flaA, genes encoding minor filament proteins, and a few nonflagellar genes that may encode proteins involved in virulence mechanisms (217,489). This transcriptional hierarchy accounts for the requirement of two alternative factors for tight and ordered control of flagellar genes for proper biosynthesis of the flagellar organelle.…”